X-79367193-G-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004867.5(ITM2A):c.23C>A(p.Thr8Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,092,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )
Consequence
ITM2A
NM_004867.5 missense
NM_004867.5 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
ITM2A (HGNC:6173): (integral membrane protein 2A) This gene encodes a type II membrane protein that belongs to the ITM2 family. Studies in mouse suggest that it may be involved in osteo- and chondrogenic differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.13239464).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITM2A | NM_004867.5 | c.23C>A | p.Thr8Asn | missense_variant | 1/6 | ENST00000373298.7 | |
ITM2A | NM_001171581.2 | c.23C>A | p.Thr8Asn | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITM2A | ENST00000373298.7 | c.23C>A | p.Thr8Asn | missense_variant | 1/6 | 1 | NM_004867.5 | P1 | |
ITM2A | ENST00000434584.2 | c.23C>A | p.Thr8Asn | missense_variant | 1/5 | 2 | |||
ITM2A | ENST00000461357.1 | n.202C>A | non_coding_transcript_exon_variant | 2/2 | 5 | ||||
ITM2A | ENST00000482194.1 | n.126C>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
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22
GnomAD3 exomes AF: 0.0000284 AC: 5AN: 176209Hom.: 0 AF XY: 0.0000163 AC XY: 1AN XY: 61309
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GnomAD4 exome AF: 0.00000823 AC: 9AN: 1092910Hom.: 0 Cov.: 29 AF XY: 0.00000558 AC XY: 2AN XY: 358464
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GnomAD4 genome Cov.: 22
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22
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.23C>A (p.T8N) alteration is located in exon 1 (coding exon 1) of the ITM2A gene. This alteration results from a C to A substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
P;.
Vest4
MutPred
Loss of phosphorylation at T8 (P = 0.0518);Loss of phosphorylation at T8 (P = 0.0518);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at